1. Field of the Invention
The present invention relates to certain novel prostaglandin compounds that are 11-substituted-16-phenoxy- and 11-substituted-16-substituted phenoxyprostatrienoic acid derivatives. The compounds of the present invention exhibit prostaglandin-like biological activities and thus are used in the treatment of mammals where the use of prostaglandins is indicated, e.g., as bronchodilators, vasodilators, and central nervous system depressants. The compounds of this invention also significantly reduce intraocular pressure without the adverse side effects of natural prostaglandins.
2. Description of the Related Art
The activity of prostaglandins and various derivatives has been described in several publications. For example, U.S. Pat. No. 4,178,457 to Van Horn, et al., describes prostaglandins having the side chains of the present invention, but lacking substitutions at the 11 carbon atom. Prostaglandins having substitutions on the 11 carbon atom, but not having the side chains of the present invention are described, e.g., in U.S. Pat. No. 3,989,744 to Woessner, et al.
In ophthalmic uses, PGE.sub.1 and PGE.sub.2 have both been shown to cause a transitory rise in intraocular pressure when first administered. Some evidence has been presented that when administered in small (5 .mu.g) does, PGF.sub.2.alpha. did not produce the initial IOP rise, suggesting that similar results might be obtained with low doses of certain other prostaglandins or their analogues [see Camaras, et al., Invest. Ophthamol. Visual Sci., December 1977, 1125-1134]. Administration of PGE.sub.1 and PGE.sub.2, even at low doses, results in severe eye irritation, the irritation response including red, swollen and watery eyes. None of the previous disclosures show the compounds covered by the generic formula of the present invention, nor their activities and the absence of side effects, as described below.